8X0S

Crystal structure of r(G4C2)2

Summary for 8X0S

• Entry DOI: 10.2210/pdb8x0s/pdb
• Descriptor: RNA (5'-R(*GP*GP*GP*GP*CP*CP*GP*GP*GP*GP*C)-3'), POTASSIUM ION (3 entities in total)
• Functional Keywords: g-quadruplex, rna
• Biological source: Homo sapiens
• Total number of polymer chains: 2
• Total formula weight: 8226.71

Authors

Geng, Y.,Liu, C.,Cai, Q.,Zhu, G. (deposition date: 2023-11-05, release date: 2024-06-19, Last modification date: 2024-07-31)

Primary citation

Geng, Y.,Liu, C.,Xu, N.,Suen, M.C.,Miao, H.,Xie, Y.,Zhang, B.,Chen, X.,Song, Y.,Wang, Z.,Cai, Q.,Zhu, G.
Crystal structure of a tetrameric RNA G-quadruplex formed by hexanucleotide repeat expansions of C9orf72 in ALS/FTD.
Nucleic Acids Res., 52:7961-7970, 2024

PubMed Abstract: The abnormal GGGGCC hexanucleotide repeat expansions (HREs) in C9orf72 cause the fatal neurodegenerative diseases including amyotrophic lateral sclerosis and frontotemporal dementia. The transcribed RNA HREs, short for r(G4C2)n, can form toxic RNA foci which sequestrate RNA binding proteins and impair RNA processing, ultimately leading to neurodegeneration. Here, we determined the crystal structure of r(G4C2)2, which folds into a parallel tetrameric G-quadruplex composed of two four-layer dimeric G-quadruplex via 5'-to-5' stacking in coordination with a K+ ion. Notably, the two C bases locate at 3'- end stack on the outer G-tetrad with the assistance of two additional K+ ions. The high-resolution structure reported here lays a foundation in understanding the mechanism of neurological toxicity of RNA HREs. Furthermore, the atomic details provide a structural basis for the development of potential therapeutic agents against the fatal neurodegenerative diseases ALS/FTD.

PubMed: 38860430
DOI: 10.1093/nar/gkae473

Experimental method

X-RAY DIFFRACTION (2.956 Å)